The functional status of the heart in cardiovascular shock remains a subject of intensive investigation and controversy due, at least in part, to the difficulty of demonstrating primary cardiac depression in the intact animal. The objective of this study is to evaluate the effects of circulatory shock on myocardial contractile function and responsiveness, utilizing isolated heart muscle preparations free from extra-cardiac in vivo influences of shock. Atrial and ventricular muscle preparations from guinea pigs subjected to endotoxic (produced by IP injection of 8 mg/kg endotoxin) or hemmorrhagic (produced by withdrawal of a percentage of total blood volume) shock will be individually evaluated in isolated tissue baths containing aerated bicarbonate-buffered Ringer's solution. Contractile function will be assessed and inotropic responsiveness to certain Ca ions -antagonistic drugs (D600, Mn ions, La ions, low Ca ion) will be compared in control and in "shocked" heart muscle to gain insight into putative cellular mechanisms whereby the shock state alters myocardial performance. Cardiac reactivity to selected chemo-therapeutic agents (e.g., catecholamines and certain antibiotics) and other inotropic interventions (hypoxia, acidosis) will be similarly evaluated. Myocardial calcium movements will be specifically assessed using tissue uptake and efflux of 45Ca. This study is designed to provide valuable information regarding cardiac function and shock-drug interactions in shock, and will suggest putative mechanisms whereby disorders of the shock state alter myocardial availability of Ca ions at a site critical to the contractile process. Such a basic alteration in calcium metabolism in the heart would have implications regarding both the pathogenesis and clinical therapy of the shock state.